Potential Tear Biomarkers for the Diagnosis of Parkinson's Disease-A Pilot Study

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. In this study, the tear proteome profile of patients with idiopathic PD (iPD, n = 24), carriers of the E46K-SNCA mutation (n = 3) and healthy control (CT, n = 27) subjects was analyzed to identify candidate biomarkers for the diagnosis of PD. An observational, prospective and case-control pilot study was carried out, analyzing the participants tear samples by nano-liquid chromatography-mass spectrometry (nLC-MS/MS) and assessing their neurological impairment. The proteomic data obtained are available at ProteomeXchange with identifier 10.6019/PXD028811. These analyses led to the identification of 560 tear proteins, some of which were deregulated in PD patients and that have been implicated in immune responses, inflammation, apoptosis, collagen degradation, protein synthesis, defense, lipid transport and altered lysosomal function. Of these proteins, six were related to neurodegenerative processes and showed a good capacity to classify patients and controls. These findings revealed that certain proteins were upregulated in the tears of PD patients, mainly proteins involved in lysosomal function. Thus, in this study, tear proteins were identified that are implicated in neurodegeneration and that may be related to an aggressive disease phenotype in PD patients.

Keywords: Parkinson’s disease; biomarkers; lysosome; tear film.

Figure 1

A STRING PPI network analysis showing the direct interactions of the biomarkers identified. The associations between the proteins shown are intended to be specific and significant, such that the proteins that interact participate in a shared activity. Splicing isoforms or post-translational modifications collapse, such that each node represents all proteins produced by a single protein-coding gene locus. (A) Protein–protein interaction (PPI) network of the proteins upregulated in PD patients relative to the CTs. (B) PPI network of the proteins downregulated in the tear fluid of PD patients.

Figure 1

A STRING PPI network analysis showing the direct interactions of the biomarkers identified. The associations between the proteins shown are intended to be specific and significant, such that the proteins that interact participate in a shared activity. Splicing isoforms or post-translational modifications collapse, such that each node represents all proteins produced by a single protein-coding gene locus. (A) Protein–protein interaction (PPI) network of the proteins upregulated in PD patients relative to the CTs. (B) PPI network of the proteins downregulated in the tear fluid of PD patients.

Figure 2

Relative biological functions of the deregulated proteins identified in PD tears expressed as a %.

Figure 3

Representation of the fold change in expression of the significant proteins when the patients included in the study were considered as iPD patients (orange), E46K-SCNA carriers (gray) or all PD patients together (blue). The same deregulated proteins appear in all three groups, but the changes in expression were stronger in the group of E46K-SCNA carriers.